Heterocyclic-substituted carbinols



Patented Sept. 6, 1949 7 2,481,377

1 UNITED STATES rATEnroFFIcE HETEROCYCLIC-SUBSTITUTED cAnBmo si Richard R. Whetstone, Berkeley, Calif., assignor to Shell Development Company, San Francisco, Calif., a corporation of Delaware I No Drawing. Application August 23, 1948', Serial No. 45,791

10 Claims. (C1.260333) 1 2 This invention relates to new chemical comwhen hydrogen directly linked to the heterocyclic pounds and to a method for their preparation. rins is replac y monovalent y ocarbon, and More particularly, the present invention relates R represents the monovalent hydrogen atom or to asymmetrically heterocyclic-substituted cara hydrocarbon group.. v binols containing in addition to the functional 5 The substituted carbi pr s d by he radical of the carbinol group another oxygengeneric formula are characterized inter alia by containin functional group. The invention retheir chemical reactivity. In part because of lates especially to new and useful carbinols conthis p p y, y Va ble as intermeditaining two separate oxygen-containing heteroates for the p p r n of re s nd o r hi h cyclic rings and an extranuclear oxygen-containmolecular weigh p e s- The Characteristics ing functional group other than the hydroXyl of of the monomers are such that improved polythe carbinol group. The invention relates particit: p uc flb p a ularly to highly reactive organic compounds which p compound of the invention, are of value as chemical intermediates, as resinformyl-3,4-dihydro-1,2-pyranyl) 2-(3,4-dihydroformers, and more generally as precursors of l,2-Dy nyl) carbi has. been found t ave numerous useful materials, properties thatmake it ofparticular interest The novel compounds to which the invention as an intermediate for the preparation of resinous relates and that are embraced within its generic polymers usefuL for example, in and as surfaceconcepts are the heterocyclic-substituted carcoating compositions. :Hardened films containbinols that may be broadly described and. defined ll'ig the polymerized n m r h v n x ellen by reference to the genericiormula lustre and an outstanding resistance to attack OH i i by organic solvents. The hardened films of polymers of this compound have an unusually good resistance to attack by alkalies and acids. Films R prepared from or containing the polymers therefore may be used with advantage as improved decorative and/ or protective coatings. The stated comp0und, and itssuitable substitution products resulting from replacement of: one or more of the nuclear hydrogenatoms by hydrocarbon groups, e. g., allcyl groups, may be polymerized in the presence of acid with polyhydric alcohols, such as glycols, glycerol and sugaralcohols, to form useful resinous. and. sub-resinous polymers which in 5 the fully hardened, i. e., cross-linked, state may be employed for the fabrication of various articles of manufacture.

Anotherv valuable group of compounds of the In this generic formula, X represents a dihydropyranyl radical. By the unmodified term a dihydropyranyl radical employed in the present specification and claims, it is intended to refer 3 to'the dihydropyranyl radicals which have one or more of the hydrogen atoms directly linked to the heterocyclic nucleus substituted by a monovalent hydrocarbon group or by monovalent hydrocarbon groups, respectively, as well as to the 3 unsubstituted dihydropyranyl radical. Y represents a member of the group consisting of (a) the radicals represented by the formulas H, H, invention comprises the ketonicheterocyclic car- 40 binols represented 2-(2-acetyl-3,4-dihydromo on H10 011 1,2-pyrany1l 2-(3,4-dihydro 1,2-pyrany1) car- 5 & binol and its nuclear hydrocarbyl-substitution products. These ketonic heterocyclie carbinols,

0 0 due to'their unique structure, may be employed 0: e 0:041 as intermediates forthepreparation of biolhydmm on ogically active compounds. For example, they 3, may be halogenated to produce useful saturated halogen-containing derivatives which may be the CH employed to combat insects and other pests.

and Their oximes also are of potential interest as biologically active materials.

By converting the formyl and the ketonic acyl group of the foregoing compounds to a carbinol carbinol v and (b) the radicals depicted by said formulas group, there are :obtained valuable dihydric When the nuclear unsaturation is eliminated, as

by saturation of the olefinic.bonds withyhydrogen, stable high molecular weight alcohols are obtained which, as such or inithe rforma-of .esters with suitable carboxylic acidsg havepropertiesadmirably adapted to use as blending agents inresinous compositions and as sofitenitifissntsfor cellulose esters and ethers.

Typical other compounds within the scope of the invention and illustrating the invention in both its generic and its -subgeneric concepts, are referred to in the following paragraphs.

It 'has been indicated 'th'at, in addition to'lthe foregoing specific carbinols, the invention includes related compounds resulting irom replacement by one-or more lrydrocarbon 'groups of hydrogen atoms bonded to carbon atoms 'o'f the respective I heterooyclic nuclei. -Broadly speaking, the substituent hydrocarbon group -'or groups may be anysuitable hydrocarbongroup-or groups. The unqualified expressionhydrocarbon group is intended to includebbththe open-chain and the cyclic hydrocarbon groups, and is --not intendedt-o be limited according to -the presence or absence ofcarbonto carbon unsaturation. Suitable hydrocarbon groups "include alkyl, aryl, alkaryl, aralkyl, cycloalkyl as well aStheunsaturated aliphatic and cycloa liphatic hydrocarbon groups. The' hyd-rocarbon groups preferably are devoid (if-aliphatic-unsaturation, i. e., they desirably are -non-ol'efinic and nonacetylenic. More specifically, the hydrocarbon groups, if 'any,linked to-the carbonatoms of "the respective hetero'cyclic nuclei preferably *are selected from "the *classromposed of the alkyl, aryl, aralkyl, alkaryl, and 'cycloa-lkyl -radicals. Although the"hydrocarbon groupswhich-maybe present may contain from one to as many as twenty carbon atoms-preferred compounds are those whichbontain, if anyflnuclear"hydrooarbyl substituent groups of 'from'bne to eight carbon atoms. Representative compounds contemplated as withirr'thegenericconcepts ofthe invention may contain hydrocarbon "substituent "groups represented by, among others, the following: methyl, ethyl, pr pyl, "isopropyl, hexyl, octyl, cyclopropyl, cyclohexyl, octade'cyl, vinyl, allyl, amyl, phenyl, lauryl, fenchyl,,menthyl, ethynyl, cyclopentenyl, styryl, phenethyl, acenaphthenyl, carvacryl, chaulrnoogrylpjcrotyl, cyclohexadienyl, and analogs an'dfhomologsi-the'reof. Hydrocarbon groups attached to theinu'clei or the substituted carbinols of the'invention .m'a'ybe'fthesame or different. Because of'thefgreater easev withwhich they maybe prepared'andjpuri'fied, and because of their especially desirable characteristics, preferred compounds arethe hereinbefore specifically -enumerated products-and the rlated products wherein-one prm-ore-"o'f the nuclear hydrogen atoms has or -have been replaced by lower alkyl groups, e. g., aikylgroups coritaining from one to eight carbon atoms; 'inoluding methyl,aethyl, propyl, butyl, amyl, hexyl,-heptyl -an'doctyl and the branched chain alkyl groups isomeric' thereto.

It is considered thata valuable group of calm :and "Y "has its zab'ove-stated significance.

4 pounds may be represented by the generic formula in which each R represents a hydrogen atom or a hydrocarbon group as hereinbefore explained, An especially valuable subgeneric group of compounds is (obtained when carbon atoms in positions' Nos. 2,-3,and 4 of the heterocyclic ring of the radical denoted by Y are substituted by hydrogen atoms only.

*Valuable substitued carbinols of the invention which'contain a formyl group as the additional oxygen-containing functional group, may be represented morespecifically .by the formula in which R has "itspreviously explained significance. As illustrative compoundshaving structures corresponding to'thisl-formula there maybe mentioned the following:

Q C-kydrocarbon in which R is 'as defined hereinabove. This formula includes the following compounds:

2 -(2-acetyl3,4-dihydro-'1;-2epyranyl) 2 -(3,4-

dihydro-1,2-pyranyl) carbinol 2- (Z-acetyl-6-methyl-3,4-dihydro-1,2-pyranyl) 2 (6-methyl-3,4-dihydro-1,2rpyranyl) carbinol 2-(2-acetyl-6-methyl-3,4-dihydro-L2-pyranyl) 2- (3,4-dihydro-1,2 pyranyl) carbinol 2 -(2 propionyl-6-ethyl-3,4-dihydro-1,2 pyranyl) 2 (6 methyl 3,4 dihydro-1,2-pyranyl) methyl carbinol 2- (2-acetyl-6-methyl 3;4 dihydro-1;2-pyranyl) 2-(6-methyl 3,4 dihydro-l,2-pyranyl) methyl carbinol Further Valuable carbinols of the invention have structures represented by the formula carbinol This formula includes the following heterocyclic-substituted carbinols: a

The novel aldehydeand keto-carbinols of the invention as a group may be prepared by condensing suitable acyl-substituted dihydropyrans in the presence of water under neutral to alkaline con ditions of reaction. The condensation may be accomplished by mixing theacyl-substituted dihydropyran with a suitable amount of water, in the presence of a basic condensation catalyst, and maintaining the mixture 'ata suitable reaction temperature. After the reaction has proceded to the desired extent,the condensation product may be recovered from the mixture in any suitable manner.

The acyl-substituted dihydropyrans which may be employed as reactants for the preparation of the substituted carbinols of the invention are those which contain an acyl substituent at the carbon atom in the No. 2position of the dihydropyran ring, and which'may have hydrocarbon radicals attached to the other carbon atoms of the heterocyclic ring, or which may be otherwise unsubstituted. Suitable acyl-substituted dihydropyrans may be represented by the formula R v 'R i RO/ o a R-O "on-R in which R represents hydrogen orhydrocarbon and R indicates acyl. Preferred substituted dihydropyrans are those in which the carbon atoms ring are unsubstituted except by hydrogen, 1. e.,- the 2-acyl-3,4-dihydro-1,2-pyrans and their. 5-.

and/or G-hydrocarbyl substitution products. Suitable substituted dihydropyrans which may be condensed according to the process of the invention include, for example, 2-formy1-3,4-dihydro- 1,2-pyran, 2 formyl-5-methyl-3,4-dihydro-L2- pyran, Z-acetyl-6-methyl-3,4-dihydro-l,2-pyran, 2-propionyl-3,4-dihydro- 1,2 -pyran, 2 -benzoyl-3,4- dihydro-1,2-pyran, 2-formyl-5eethyl-3,4-dihydro 1,2-pyran, and their homologs and their analogs. The acyl-substituted dihydropyrans may be pre-. pared in any suitable manner, as by condensing by heating one or more conjugated vinyl aldehyde and ketones (alpha,beta-olefinicaldehydes and ketones) in the liquid state,preferably at about 150 C. to about 250 C., in the presence of a polymerization inhibitor or by ring closure of suitable aliphatic substituted aldehydes or ketones. One or a plurality of the acyl-substituted dihydropyrans may be employed in accordance with the process of the invention.

Basic condensation catalysts which may be used to accelerate the condensation of the acyl-substituted dihydropyrans preferably are those water-soluble substanceswhich impart alkalinity to water, the inorganic bases and alkaline salts being especially suitable. The caustic alkalies, such as the alkali metal hydroxides and carbonates, and the alkaline earth metal hydroxides, are eminently satisfactory. Sodium hydroxide, potassium hydroxide, lithium hydroxide, caesium hydroxide, sodium carbonate, potassium carbonate, calcium hydroxide, barium hydroxide and even strontium hydroxide may be mentioned as suitable alkalies, the alkali metal hydroxides being preferred. Basic-reacting salts may be employed as the condensation catalyst. Suitable salts include, for example, sodium acetate, sodium bicarbonate, trisodium phosphate, trisodium citrate, sodium borate, etc. The condensation catalyst is employed in aqueous solutions. Solutions of the catalyst having a concentration from about 0.005 gram-equivalents per liter to about 5 gramequivalents per liter may be used in the general case. A preferred range of concentrations is from about 0.005 to about .5 gram-equivalent per liter.

According to the process of the invention, the condensation of, the acyl-substituted dihydropyrans is carried out in the presence of water. It is essential to'employ such an amount of water that the desiredreaction occurs, but'under the reaction conditions to avoid thepresence of water i in amounts that would lead to deleterious side reactions or to the formation of undesired polymers. The amount of Water may be varied from about 1 mole to about 100 moles per. mole of the acyl-substituted dihydropyran. A preferred range is from about 10 moles to about moles of water per mole of the substituted dihydropyran. More particularly, when an aqueous solution containing from about 0.005 to about .2 equivalent per liter vof a. caustic hydroxide is employed, amounts of the solution containing from about 10 to about 50 moles of water per mole of the substituted dihydropyran maybe employed with eminently satisfactory yields of and conversions to the desired condensation product.

The acyl-substituted dihydropyrans employed in the process of the invention are potentially capable of reacting with or in the presence of water to form various products other than those desired in accordance with the invention. Thus, reaction at the nuclear olefinic bond may occur to iorm hydrates o f the acyl-substitute'ddihydropyrans. n' -fa'ct,' ieven the heterocycli'c ring of the acyFstibstituted dihydropyrans is prone to hydr'ol-y'sis, suoh hydrolysis or opening of the ring forming "acyclic products quite unlike the prod nets desired' m accordance with the invention. It has been "unexpectedly discovered in accordance \iiith therpr esent invention-that the occurrence of these and otherpossible"undesired side reactions may b'esubstantially avoided by conducting the con ehsation of "the '-acyl'substituted dihydropyrans' in'the presence o'f'water and a basic conderisaition catalyst, ?as' aforesaid. The basic condensati'o" catalyst appears to have not only an activating efiedtupon the "desired reaction, but also to h'ave an inhibiting-or restraining influence upon' u ndes'ired side' reactions, since in its absence the aeyl substituted dihydropyrans employed in the pi o'cess of the inventiontend to react to form preddmiriaritly products other than the desired substituted 'c'arbin'ols.

'Thedesiredcondensation reactions'occur at any suitable temperature above about 0., up to a temperature -"fihatTcauses undesired polymerization of the -or gan ic reactant or other reactions in excessive :amounts. Temperatures of from about I013fto about l" C.:may:beused advantageously. The desired condensation of the a'cyl-substituted dihydropyrans feIn-p'l'oyed in the process of the invention may be effected efficiently at or about ordinary roomPtemp'e'ratures"(20 'C. to 40 0.), \vith the advaritage that necessity for means to co'ol and/oriheatthereacting mixture is obviated.

.ran i'lll'lstrationtof the products and process of-the'im ention,:2iformyl23A-dihydrm1,2-pyran wasmixed' at about Crw'ith about 4.5 times its weight o'f'water containing 'in solution 25 grams 0625 more? T of?sodiumthydroxide per liter. After -a "few minutes, iinsoluble material began to separate"=-from the mixturegand atter minutes the-characteristic. o'd'or ofthe :formyldihydropyran ooiild not b'e :detected. The water was decanted 'from'the insolublei m'aterial and the latter was iiissolved in ether-fbenzene mixture. The solution wvas wash'ed with' water' and then distilled under about 2 millimeters mercury pressureto a kettle temperature of 100 0., thereby removing the solvents; anyremaining 'Watenan'd other low-boil- :in'g materials. Kline-remaining residue amounted *to '7 2'% by' w'e'i'ght on"- the amount of formyl-dihydropyran employed. It was a'rli'ght yellow viscous liquid shown by analysis to consist essentially of the desined' product :2- 2eiorm'yl-3 ,'4-dihydro- 1,2- pyranyl) 2='(3;4:dihydro 1;2 pyranyl) carbinol of the structure 7 The Y:

8 o'fithei roducttoiincreaseiinwiscosity uponstand ing, indicating spontaneous polymerization.

vvh'enithe "foregoing condensation 'was effected in saturated aqueous isodium carbonate solution at room temperature, the insoluble product formed almost immediately. In saturated aqueous sodium bicarbonatesolution,.the formation of the insoluble product wasless'rapi'd, about'90 minutes being required forxsubstantial completion of the condensation.

As a further illustration of the invention, 2- acetyl-6-methyl-3,4-dihydro-1,2-pyran may be mixed -at about room temperature with a dilute aqueous solution of potassium hydroxide, :and'the mixture warmed to about 40 .C. .After the reaction has occurred, the product is'wo'rked up in the manner employed .inthepre'ceding example. The desired product is "ioumi to be "2-(2 -'ac'etyl-6- methyl-3,4-dihydro iL2-pyrany1) i2- (G-methyl- 3,4-dihydro-"12--pyranyl) imethy'l carbinol, of the structure H2 no CH2 on mo CH3(% (IJH [C As indicated Joy-the "foregoing experiments, the condensation of the :acyl-subst'ituted dihydropyrans toformthexdesired products may be carried out by mixing with water in a suitable amount, in the presence of a basic condensation catalyst, and allowing the mixture to stand for a suitable time. "The mixture may be prepared by mixing the ingredients in any order. After the reaction hasfoccurre'd, -the'products may be recovered and/or purified in any desired manner. Methods of recovery and purification which are suggested include distillation, for example, socalled -molecular idistillatiom crystallization from solvents, adsonption, treatment with selective solvents/etc.

As chemicalintermediates, the carbinols of the invention are-versatile and useful. For example, 2- 2-formyl-3 ;4'-"dihyd-ro-:1-,2,-,pyranyl) 2- (3,4-dihydro-1,2-1pyr-anyl) :carbinoLmay-be hydrogenated to :the saturated dihydroxylic compound '2-(2- methyloltetrahydropyranyl) 2-tetrahydropyranyl :carbinol which may ibeused'as a plasticizer and 'as' a special solvent. "By treatment with water in the'presence of acid :and-catalytically activated hydrogen, the 2- 2-formyl-3,4dihydro- 1,2- pyranyl) 2 t3fl dihydro-iflmyranyl) carbinol may be converted 'tonovel rypolyhydric alcohols, such as 5-.methylol-:lJ,5;6,'7;1-1-hendecanepentol and "7-methylol 1-;56;1 1-hendecanetetrol. Esters of "these polyhydric alcohols with idrying oil acids have desirable and improved properties for use in surface-coating*compositions, e. ;g., paints and Havingi'described"theinvention in various of its specific :and sgeneric embodiments, it will be apparent that modifications in detail thereof may be made by those skilled in" the art without departing from the letter and spirit of the invention as it is defined inthe hereto appended claims.

I claim as my invention:

1. 2- (2-formyl-3A-dihydro-1.2-pyranyl 2-(3,4- dihydro-LZ-pyranyl) carbinol.

methyl .carbinol.

10 3. 2-(2-methylol-3,4-dihydro-L2-pyranyl) 2- of (a) the radicals represented by the formulas (3,4-dihydro-L2-pyranyl) carbinol.

4. Carbinols of the structure 1110 \GH 1120 \CH H: H: H R-("l on, (3H mo |C'R l o l O R-C CH-C-JJ C-R 0= --monovalent 0: H

\ I hydrocarbon H carbinol 02 in which each R represents a member of the H OH group consisting of hydrogen and monovalent and J; hydrocarbon.

5. Carbinols of the structure 15 carbinol 5 5' and (b) the radicals depicted by said formulas R OH H when hydrogen directly linked to the heterocyclic I 2 ring is replaced by monovalent hydrocarbon, and RO CH(l3--C 0- 0 R represents a radical selected from the group H consisting of hydrogen and monovalent hydrocarbon.

8. A process of preparing 2-(2-formyl-3,4- in which each R represents a member of the f -L -Pl y py ny group consisting of hydrogen and monovalent carblml Whlch comprises miXmg y1- A- CHO hydrocarbon dihydro-1,2-pyran with an approximately 0.0625 carbinols f the structure N aqueous solution of sodium hydroxide at about 25 C., separating insoluble product from the 13, 5a mixture, and heating the separated insoluble product to remove volatiles boiling below the boil- 011 E20 (PR ing point of said 2-(2-formyl-3,4-dihydro-1,2- LR pyranyl) 2-(3,4-dihydro-L2-pyranyl) carbinol.

\ g 9. A process of preparing 2-(2-formyl-3,4-dihydro-1,2-pyranyl) 2-(3,4-dihydro-L2-pyranyl) carbinol which comprises condensing 2-formyl- 3,4-dihydro-L2-pyran in an aqueous solution of an alkali at a temperature from about 10 C. to about 75 C.

in which each R represents a member of the group consisting of hydrogen and monovalent hydrocarbon.

10. A process of preparing a heterocychc-sub- Carbmols of the Strucfiure 40 stituted carbinol which comprises condensing an 011 acyl-substituted dihydropyran having an acyl J group in position No. 2 of the dihydropyran ring in an aqueous solution of an alkali at a temperature of from about 10 C. to about C.

in which X represents a dihydropyranyl radical, RICHARD WHETSTONE' Y represents a member of the group consisting No references cited. 

